Epstein‐Barr virus (EBV) nuclear antigen (EBNA) 1 is perhaps the most widely studied EBV protein, because of its critical role in maintaining the EBV episome and its expression in all EBV‐associated malignancies. Much of this research has focused exclusively on the EBV wild‐type (wt) strain (B95‐8). Sequence analysis of the gene encoding for EBNA1 in EBV isolates from 43 Caucasians has now revealed considerable EBNA1 sequence divergence from the EBV wt strain in the majority of isolates from this population group. Importantly, T cell recognition of an endogenously processed HLA‐B8–binding EBNA1 epitope was greatly influenced by this sequence polymorphism.